Title

Identifier

Author

Degree

Doctor of Philosophy (PhD)

Department

Biological Sciences

Document Type

Dissertation

Abstract

Viruses are tiny intracellular parasites that often cause devastating diseases on cellular organisms. To suppress viral infection, cellular organisms have evolved a wide spectrum of antiviral defense mechanisms. Antiviral RNA interference (RNAi) is one of the antiviral mechanisms conserved in eukaryotes. During antiviral RNAi, the destruction of invading viral RNAs is mediated by small interfering RNAs derived from the viral replication complex, in the form of double-stranded RNA (dsRNA). Because of its sequence-specific nature, antiviral RNAi can also target host homologous transcripts, for instance leading to disease syndromes in plants. As a counter-defense mechanism, many viruses produce RNAi suppressors that suppress RNAi through distinct mechanisms. So far, RNAi-mediated virus-host interactions have remained largely unexplored in the nematode worms which are known to have a unique RNAi gene constitution. As a result, whether virus-derived siRNAs (viRNAs) are able to direct worm gene silencing, whether heterologous viral suppressors are still functional in nematode worms and how the worm-specific RNAi genes contribute to antiviral RNAi remain open questions. In this thesis I describe my exploration of several aspects of RNAi-mediated virus-host interaction in the nematode Caenorhabditis elegans. Through the study of virus-induced gene silencing in C. elegans I found that viRNAs can target and silence host genes. This is the first demonstration that viRNAs have the potential to silence host gene expression in the animal kingdom. Since certain viral suppressors that inhibit viRNA function without a size reference become resistant to RNAi but some suppressors that specifically suppress the function of 21-nucleotide (nt) viRNAs still sensitive to RNAi, I conclude that 21-nt viRNAs do not play a major role in worm antiviral RNAi. My study on the function of a worm-specific RNAi gene, called rsd-2 (RNAi spreading defective 2), suggested that antiviral RNAi in C. elegans can be initiated in the absence of a dsRNA binding protein, which is in sharp contrast to that in plant and insect systems. Through functional domain swap and viRNA profiling, I found that RIG-I-like RNA helicases contribute to worm antiviral RNAi through distinct mechanisms with one of them contributing to virus detection.

Date

2013

Document Availability at the Time of Submission

Secure the entire work for patent and/or proprietary purposes for a period of one year. Student has submitted appropriate documentation which states: During this period the copyright owner also agrees not to exercise her/his ownership rights, including public use in works, without prior authorization from LSU. At the end of the one year period, either we or LSU may request an automatic extension for one additional year. At the end of the one year secure period (or its extension, if such is requested), the work will be released for access worldwide.